Mucolipin-1 (MCOLN1)

Mucolipin-1 (MCOLN1, also commonly referred to as TRPML1) is a lysosomal ion channel belonging to the transient receptor potential (TRP) channel superfamily[1][4][5]. This protein is a non-selective, pH-regulated cation channel residing primarily in lysosomal and late endosomal membranes, where it mediates release of Ca²⁺ and other ions (including Fe²⁺, Na⁺, K⁺, H⁺, Mg²⁺) into the cytosol[1][3][4][5]. MCOLN1 is crucial for lysosomal acidification, membrane trafficking, lysosomal exocytosis, autophagy, and metal ion homeostasis[3][4][5]. Mutations in the MCOLN1 gene cause mucolipidosis type IV, a rare autosomal recessive lysosomal storage disorder marked by severe neurodegeneration, visual impairment, and cellular accumulation of storage vacuoles[1][2][4][5]. As an essential regulator of the lysosome, MCOLN1 is considered a valid therapeutic target for disorders rooted in lysosomal dysfunction and is being studied for its broader implications in neurodegeneration, immunity, and cancer[1][3][4][5].

Other names

Mucolipin TRP cation channel 1TRPML1ML4MLIVMG-2MucolipidinTransient receptor potential mucolipin 1Transient receptor potential channel mucolipin 1Mucolipidosis type IV protein

Direct agonists (e.g., ML-SA1, MK6-83): Activate the TRPML1 channel to promote lysosomal Ca²⁺ release, enhancing exocytosis, autophagy, and membrane repair[1]. Indirect modulation via cell signaling pathways (e.g., mTOR/TFEB, PKA) Modulation by phosphoinositides and reactive oxygen species[5]