TMEM63C is an osmosensitive calcium-permeable cation channel that functions as a mechanosensitive ion channel activated by hypotonic stress 1. Unlike TMEM63B, it lacks phospholipid scramblase activity. The protein localizes to the endoplasmic reticulum and is particularly enriched at mitochondria-ER contact sites, where it regulates metabolite flux and organellar morphologies in response to osmotic changes 2. TMEM63C plays a critical role in regulating mitochondrial and ER morphology and may control mitochondrial motility in motor neuron axons 2. In kidney podocytes, TMEM63C expression is regulated by microRNA-564 and transforming growth factor-beta, with reduced expression linked to epithelial-mesenchymal transition and altered cell viability 3. TMEM63C functions as a pro-survival factor in podocytes under angiotensin II stimulation through NFκB-dependent mechanisms 4. Functionally, it is essential for glomerular filtration barrier integrity 5. Clinically, biallelic TMEM63C variants cause autosomal recessive spastic paraplegia 87, characterized by progressive lower-limb spasticity and motor neuron degeneration, sometimes accompanied by mild intellectual disability 21. Additionally, TMEM63C has been identified as a candidate gene associated with early-stage Alzheimer's disease biomarkers 6.