ML-SA1 (Mucolipin-specific synthetic agonist 1) is a potent synthetic agonist for TRPML1.
ML-SA1 induces significant [Ca2+]cyt increases in HEK293 cells stably- or transiently-expressing ML1-4A.
ML-SA1 targets all three TRPMLs, the expression levels of TRPML2 and TRPML3 are very low, and TRPML1 is the predominant lysosomal TRPML channel.
ML-SA1 induces TRPML1-mediated Ca2+ release from lysosomes.
ML-SA1 and TRPML1 overexpression rescue the trafficking defects and reduce cholesterol accumulation in NPC cells.
