TMEM38B encodes TRIC-B (trimeric intracellular cation channel type B), a ubiquitously expressed endoplasmic reticulum (ER) monovalent cation channel essential for intracellular calcium homeostasis 1. TRIC-B functions as a potassium counter-ion channel activated by elevated cytosolic calcium, enabling rapid calcium release from intracellular stores and maintaining synchronized ER-cytoplasm calcium signaling 2. In osteoblasts, TRIC-B is critical for regulating ER calcium flux, collagen I synthesis, and osteoblastic differentiation 3. Loss of TMEM38B function impairs intracellular calcium homeostasis and collagen synthesis, disrupting bone mineralization and osteocyte function 1. TMEM38B mutations cause Osteogenesis Imperfecta type XIV, a rare autosomal recessive skeletal dysplasia characterized by low bone mass, recurrent fractures, bone deformities, and variable clinical severity 4. Affected individuals present with muscular hypotonia, skeletal deformities, and growth retardation, though hearing and dentition are typically unaffected 5. Mechanistically, TMEM38B loss disrupts the osteocyte lacuno-canalicular network and impairs osteocyte maturation 1. While bisphosphonates provide moderate therapeutic benefit, innovative therapies are needed given persistent fracture risk 4.