TMEM214 is a transmembrane protein localized to the outer membrane of the endoplasmic reticulum (ER) that functions as a critical mediator of ER stress-induced apoptosis 1. Its primary mechanism involves acting as a scaffolding anchor for recruitment and activation of procaspase 4 to the ER; TMEM214 overexpression induces apoptosis while knockdown inhibits ER stress-induced apoptotic signaling 1. The protein constitutively associates with procaspase 4, and both proteins are essential for apoptosis following ER stress caused by misfolded protein aggregation 1. Clinically, TMEM214 dysfunction has been associated with autism spectrum disorder (ASD) in human populations, with biallelic variants identified in Pakistani families with genetic enrichment for recessive inheritance patterns 2. Additionally, TMEM214 DNA methylation in umbilical cord tissue correlates with gestational weight gain and may serve as an early epigenetic biomarker for offspring obesity risk, suggesting broader developmental implications 3. In muscle tissue, TMEM214 represents one of several nuclear envelope proteins examined in Emery-Dreifuss muscular dystrophy, though it showed variable distribution patterns across patient samples without consistent diagnostic utility 4. These findings indicate TMEM214's multifaceted roles in cellular stress responses and developmental programming, though additional mechanistic studies are needed to clarify its full pathophysiological significance.