Mucolipin-3 (MCOLN3)

Mucolipin-3 (MCOLN3), also known as TRPML3, is an inwardly rectifying, nonselective cation channel encoded by the MCOLN3 gene in humans[1][4]. It is a member of the mucolipin (TRPML) subfamily within the large TRP ion channel family, with six transmembrane domains and significant permeability to Ca2+, Mg2+, Na+, and K+[1][2][5]. MCOLN3 primarily localizes to late endosomes and lysosomes, contributing to the regulation of intracellular calcium signaling, endosomal/lysosomal acidification, organelle trafficking, and autophagy[4][5][3]. Functional alterations—especially dominant-activating mutations—lead to hair cell death and deafness, as well as pigmentation changes in model animals[2][3]. The protein plays a crucial role in vesicular ion homeostasis and is thought to underlie specialized functions in cell types with particular lysosomal demands. MCOLN3 has been linked to neurodegenerative and pigmentary phenotypes but is not itself a major driver of common human disease. Selective small-molecule agonists (such as SN-2) and the non-selective agonist ML-SA1 are tool compounds, but there are no known therapeutic drugs directly targeting MCOLN3 in clinical use[1].

Other names

Mucolipin TRP cation channel 3TRPML3Transient receptor potential channel mucolipin 3FLJ11006TRP-ML3mucolipin 3

Agonists (channel activators) open the MCOLN3 channel, increasing Ca2+ release from endolysosomes[1]