1.A.5.3.1
The lysosomal monovalent cation/Ca²⁺ channel, TRP-ML1 (Mucolipin-1) (associated with the human lipid storage disorder, mucolipidosis type IV (MLIV)) (Kiselyov et al., 2005; Luzio et al., 2007). TRPML1 is an endolysosomal iron release channel (Dong et al., 2008).  It interacts with TMEM163, a CDF heavy metal transporter (TC# 2.A.4.8.3).  Together these proteins function in Zn²⁺ homeostasis, possibly by exporting Zn²⁺ (Cuajungco et al. 2014).  The MLIV disease could result from Zn²⁺ overload.  TrpML1 is probably involved in Zn²⁺ uptake into lysosomes (Cuajungco and Kiselyov 2017). Asp residues within the luminal pore may control calcium/pH regulation. A synthetic agonist, ML-SA1, can bind to the pore region to force a direct dilation of the lower gate (Schmiege et al. 2018). This channel plays a role in vesicle contraction following phagocytosis or pinocytosis, allowing maintenance of cell volume (Freeman et al. 2020). A mutation gave rise to progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images (Hayashi et al. 2020).