Tmem63c, a member of the TMEM63 family, encodes a predicted osmosensitive calcium-permeable cation channel. The TMEM63 family proteins are involved in various physiological functions, and Tmem63c, in particular, may be associated with osmoregulation-related pathways. Dysfunction of this gene is linked to several diseases, highlighting its biological importance. Genetic models, such as mouse models, are valuable for studying Tmem63c [1,4].

In humans, biallelic variants in Tmem63c are associated with hereditary spastic paraplegias, sometimes accompanied by mild intellectual disability. Biochemical and microscopy analyses in cellula studies show that Tmem63c is an endoplasmic reticulum-localized protein, enriched at mitochondria-endoplasmic reticulum contact sites, and plays a role in regulating both endoplasmic reticulum and mitochondrial morphologies [1]. In human podocytes, Ang II can induce Tmem63c expression, possibly via NFκB-dependent mechanisms. Down-regulation of Tmem63c reduces cell viability, indicating it is a potential pro-survival factor [2]. Also, miR-564 can reduce Tmem63c expression, while TGF-β treatment leads to increased expression. Reduced Tmem63c expression is associated with changes in epithelial-mesenchymal transition (EMT) marker proteins and decreased cell viability in renal cells [3]. In zebrafish, tmem63c has a role in mediating the glomerular filtration barrier function [5].

In conclusion, Tmem63c is essential for maintaining normal cell functions, especially in processes related to endoplasmic reticulum and mitochondrial morphologies, cell viability, and glomerular filtration barrier function. Research using model-based studies, including those on human cells and zebrafish, has revealed its significant contributions to diseases such as hereditary spastic paraplegias and kidney-related disorders, providing insights into the underlying molecular mechanisms.