MARCHF6 is a large multi-pass E3 ubiquitin ligase embedded in the membranes of the endoplasmic reticulum. It participates in endoplasmic reticulum associated degradation, including autoubiquitination, and many of its identified substrates are involved in sterol and lipid metabolism. Post-translationally, MARCHF6 expression is attuned to cholesterol status, with high cholesterol preventing its degradation and hence boosting MARCHF6 levels. By modulating MARCHF6 activity, cholesterol may regulate other aspects of cell metabolism beyond the known repertoire. Whilst we have learnt much about MARCHF6 in the past decade, there are still many more mysteries to be unravelled to fully understand its regulation, substrates, and role in human health and disease.

MARCHF6是嵌入内质网膜中的大型多遍E3泛素连接酶。它参与内质网相关的降解，包括自体泛素化，并且其许多已鉴定的底物都参与固醇和脂质代谢。翻译后，MARCHF6的表达被调至胆固醇状态，高胆固醇阻止其降解，从而提高了MARCHF6的水平。通过调节MARCHF6活性，胆固醇可以调节细胞代谢的其他方面，而不是已知的所有功能。在过去十年中，我们已经了解了很多有关MARCHF6的知识，但是，要充分了解其调控，底物以及在人类健康和疾病中的作用，还有许多谜团尚待阐明。