TMEM94, also known as ERMA, is an essential component involved in Mg2+ transport. It is an ER-localized protein with features analogous to P-type ATPases, uniquely combining a P-type ATPase domain and a GMN motif for Mg2+ uptake into the endoplasmic reticulum (ER), which is a major intracellular Mg2+ compartment [1]. It may also be involved in other biological processes considering its associations with various disease-related phenotypes.

In mouse models, loss of Tmem94 generated by Nuclease technology was embryonic lethal and led to craniofacial and cardiac abnormalities as well as abnormal neuronal migration pattern, suggesting its importance in craniofacial, cardiovascular, and nervous system development [4]. Biallelic pathogenic variants of TMEM94 are associated with intellectual developmental disorder with cardiac defects and dysmorphic facies (IDDCDF), characterized by global developmental delay, intellectual disability, speech delay, congenital cardiac malformations, and dysmorphic facial features [2]. Decreased TMEM94 expression inhibited pancreatic cancer cell proliferation and migration, indicating its potential role in pancreatic cancer development [3].

In conclusion, TMEM94 is crucial for Mg2+ uptake in the ER. Mouse models with Tmem94 knockout have revealed its significance in craniofacial, cardiovascular, and nervous system development. Its involvement in diseases like IDDCDF and pancreatic cancer highlights the importance of studying TMEM94 for understanding disease mechanisms and potentially developing new treatment strategies.