TMBIM4 is an anti-apoptotic protein that regulates intracellular calcium homeostasis and cell survival through its function as an ion channel. The protein localizes to multiple cellular compartments, including the Golgi apparatus, endoplasmic reticulum, and plasma membrane, where it modulates both capacitative calcium entry and inositol 1,4,5-trisphosphate-mediated calcium release. TMBIM4 confers resistance to diverse apoptotic stimuli and promotes cell migration and invasion through store-operated calcium signaling 1. TMBIM4 is ubiquitously expressed across tissues and is essential for cell viability 2. Disease relevance spans multiple pathways. In congenital heart disease, deleterious TMBIM4 variants cause cardiac heterotaxy through impaired left-right patterning during gastrulation, with depletion leading to embryonic depolarization and abnormal pluripotency exit 3. TMBIM4 deficiency facilitates NLRP3 inflammasome activation and trophoblast pyroptosis in preeclampsia, with TMBIM4 expression significantly decreased in affected placentas compared to normal pregnancy 4. In age-related cataracts, microRNA-125a-3p suppresses TMBIM4 in lens epithelial cells under ultraviolet radiation, promoting apoptosis and reducing cell viability 5. TMBIM4 has also been associated with blood pressure variation in African-ancestry populations 6. These findings identify TMBIM4 as a plausible therapeutic target in developmental, inflammatory, and degenerative disease contexts, though clinical translation remains in early stages.