TMEM94 encodes a P-type ATPase transporter localized to the endoplasmic reticulum (ER) that mediates magnesium ion (Mg2+) uptake from the cytosol 1. The protein contains characteristic P-type ATPase domains including actuator, nucleotide, and phosphorylation domains, with a unique GMN motif essential for ER-Mg2+ uptake, and a conserved tyrosine residue critical for Mg2+ binding 1. TMEM94 functions in intracellular magnesium homeostasis by replenishing the ER as a major intracellular Mg2+ compartment 1. Biallelic loss-of-function TMEM94 variants cause intellectual developmental disorder with cardiac defects and dysmorphic facies (IDDCDF) 23. Affected individuals present with global developmental delay, intellectual disability, congenital heart defects, and distinctive facial dysmorphism including triangular face, deep-set eyes, broad nasal root, and hypertelorism 3. Cardiac pathology involves dysfunction through haploinsufficiency and abnormal Ca2+ cycling in cardiomyocytes 1. Gene expression analysis reveals reduced TMEM94 mRNA in affected individuals, with dysregulation of genes essential for cell growth, proliferation, and survival 3. Mouse models with loss of Tmem94 show embryonic lethality with craniofacial, cardiac abnormalities, and abnormal neuronal migration 3, establishing TMEM94's critical role in early development of the nervous, cardiovascular, and craniofacial systems.