For centuries, till the rise of Tibet as a potent political entity around 1650, Ladakh was literally the last outpost of Buddhism in the world – the sort of outpost where religion was modelled to suit the needs of the day, not a rigid structure carried down generation after generation. Tibet rose as a political power and even then, it looks as if Ladakh and Tibet didn’t fight in the name of religion – they just complemented each other, with Ladakh supporting the Brug-pa school while Tibet supported Gelug-pa. Both the schools and other minor schools of thought maintained presence everywhere and all the schools were widely respected. There were feuds sometimes, as like the one of Tibetan invasion of Ladakh in 1679 where Ladakh and Bhutan sided together against Tibet. 
Though all history, Ladakh’s case was a fight with it’s neighbours Kashmir, Baltistan, Yarkand, Guge, Tibet and the hill states of the current Himachal Pradesh except for the Mughal interlude where the Mughals occupied Kashmir. When Kashmir fell, it’s but obvious that attempts will be made on the next kingdom in the line. 
All of this started when Jamyang Namgyal tried to interfere in a dispute between two chiefs of Purig. The Magpon of Skardu, Ali Mir entered the fight against Ladakh. Whole of Ladakh was pillaged with much destruction to religious property before the Balti army retreated. The king was kept in honourable custody but he made Ali Mir’s daughter pregnant. Ali Mir, with no option, released the king and married him off to his daughter. The Balti king lost control of Purig but the Balti control over Ladakh stayed till the end of Ali Mir’s reign. The Ladakhi king, ashamed, turned religious. 
His son, Sengge Namgyal tried to assuage the situation by invading Cigtan but the invasion was a failure – Gaga Tsanpa, the leader of the expedition was captured while the nephew and niece of the ruler of Cigtan who were in Ladakh were detained. A truce was brokered by Taktsang Gyatso by exchange of prisoners.  However, the Mughal accounts state that on invasion of Sangi Bamkhal of Purig, Adham Khan, now a Mughal vassal solicited the aid of Ali Mardan Khan, the governor of Kashmir. He sent Husain Beg along with a massive army. The combined armies defeated Sengge in 1639 and he retreated to the fort of Karpu. To escape the siege, he accepted vassalage, the terms of which Sengge Namgyal never bothered to fulfil. 
In 1663, Aurangzeb visited Kashmir. Fearing retribution, the Ladakhi king sent a voluntary embassy professing vassalage and with the promise of a mosque built and qutba read. It is possible the embassy is not voluntary but was sent on the face of an imminent invasion. When nothing was done by Ladakh, an envoy Mohammed Shafi was sent with a request for construction of mosque and conversion to Islam at the threat of an invasion. The king was called the Zamindar of Greater Tibet. Qutba was read, foundations of a mosque were laid and steps were taken to diffuse Islam among the population. A heavy tribute was paid. The king was given a Muslim name Aqibat Hussain Khan.
In the 1679 Tibetan invasion of Ladakh as a part of the feud between Brug-pa and Gelug-pa schools of Buddhism where the Tibetans took even the Ladakhi capital city with the king running the show from Tingmosgang, the Ladakhi king asked the intervention of Kashmir. Fidai Khan was sent by the governor Ibrahim Khan who was reinforced by Purig, the Baltis and levies in lower Ladakh. In the Battle of Bagso, the Tibetans were defeated and chased into Guge. Fidai Khan extracted the charges and pending tribute, the king converted, under the name of Aqibat Mahmud Khan before Fidai Khan left. Along with that, one of his sons was to be sent to Kashmir as a hostage. The only territorial change was the village of Nabsat. However, Tibet invaded again after the Mughals left and destroyed the Leh Fort before the king surrendered. 
The Tibetans faced two problems now – a Mughal vassalage means Mughals can penetrate into Tibet proper if provoked and the king is a Muslim convert and can do serious harm to the religion. Tibet initiated the peace discussions with the condition that the king reconvert to Buddhism, which he did. The territorial change involved was annexation of Guge and Spiti. This war was the end of Ladakh as a local power. It’s a matter of providence that Mughals and Tibetans who will eventually be supported by the Dzunghars and China didn’t clash.
After the case of Jamyang Namgyal, there are many cases of Ladakhi kings taking Muslim wives but, generally, they never involved in power politics, but with very rare exceptions.
After the death of Nima Namgyal, his second wife, the daughter of Hatim Khan demanded her son Krasis Namgyal to be made the king as against the heir designate. He was given a separate tract in Purig area and was installed in 1734. All was well when the brothers ruled but the situation deteriorated after the king changed. Around 1750, there was a quarrel between the Ladakhi king Phuntsog Namgyal and his uncle Krasis Namgyal. Ladakh and Skardu joined forces to take Shigar and before the fight became bitter, in 1750, the Dalai Lama advised peace. But, both of them sent requests to help from Kashmir. The Mughal governor sent forces but the Dalai Lama, fearing Muslim interference, coerced peace between the both. The Mughal Governor asked for a combined attack on Purig by Ladakh and Kashmir when Krasis Namgyal is away. Fully knowing of the Battle of Manupur(1748) where the Mughal army was defeated by Ahmad Shah Abdali and that Kashmir is not in a position to send an army, the Tibetan mediator, Katog Rigdzin Tsewang Norbu asked for an envoy as well. The pact was signed in 1752. It was decided that no two kings should exist in Ladakh and all the brothers of the eldest should be ordained as monks. Krasis Namgyal will rule till his death and after that, his kingdom of Purig will be annexed to Ladakh. Status quo on trade was promised for the Kashmiris.
The king Tsewang Namgyal fell into the influence of a low class Muslim woman whom he married. She was deridingly called Bhemo Gyal. She got the top nobles arrested and executed and got her brother Nasib Ali made the Prime Minister, after the Prime Minister is executed. There was an open rebellion where the royal palace was stormed– the Muslim wife is killed and possibly her brothers, but the king was not touched. He married a princess of Sod, but later in life, he got influenced by her, a Shia. He revived the old title Aqibat Mahmud Khan and stopped the religious practices in Leh. Having induced into buying horses by a Muslim trader, his penchant for horses strained the economy much to the level that he hired a Muslim goldsmith to mint silver coins in the Muslim fashion to fund his extravagance in 1781. There was another rebellion in response and the king abdicated the next year.
After that, we don’t see any Muslim interference in Ladakhi politics except for some border wars involving Baltistan and nothing more.
Even if Muslims stopped interfering, one can say fate didn’t allow that to happen, for, one can argue, the Ladakhi dynasty as a ruling entity ended due to a Muslim curse.
In 1826, a scion of the Yarkand Khojas led an invasion to retake his ancestral lands. After seeing some initial success, he was captured. His troops under Abdus Sattar, a prince of Kokhand retreated into Ladakh with terrible losses. The band of 300 out of the original 1000 were provided succor and Abdus Sattar was accorded the treatment of the head of a visiting ruler. A few of his followers left for Haj and the rest under Abdus Sattar settled in Leh. The king, to avoid any trouble from the Chinese, congratulated the Chinese of their victory and apprised them of the fugitives. China asked them to be extradited. Before even the Dalai Lama could know and intervene in their behalf, they were taken into Tibet and executed. It seems Ladakh allowed many of them to slip away and of the 102 delivered, 45 escaped, 19 died of illness and 38 executed in two batches. The refugees cursed the royal family, death by smallpox for the betrayal and the dynasty ended formally after the last king died of small pox as a Dogra commander.