Tmcc2, transmembrane and coiled-coil domain 2, is an endoplasmic reticulum-residing transmembrane protein. It is involved in multiple biological processes. In erythropoiesis, it is crucial for normal red blood cell maturation. In the inner ear, it plays a role in the development and function of auditory hair cells. It also has associations with neurodegenerative diseases through its interactions with proteins like amyloid protein precursor (APP) and apolipoprotein E (apoE) [1,2,3,4].

Gene knockout studies have provided significant insights. In Tmcc2 -/- mice, neonatal macrocytic anemia with numerous nucleated red blood cells (nRBCs) and occasional multinucleated RBCs was observed. There were cytoplasmic intrusions into the nucleus and double membranes in nRBCs, and fewer erythroid cells were enucleated. In adults, there was mild polycythemia with active extramedullary erythropoiesis in the spleen, and a defect in erythroid maturation at the polychromatic to orthochromatic transition stage. In Tmcc2 knockout mice in the context of the inner ear, congenital hearing loss and progressive auditory hair cell loss were found, with increased endoplasmic reticulum stress [1,2]. In Drosophila, disruption of the orthologue Dementin affected neurodegeneration, with accumulation of APP-like protein fragments and pathological features resembling early-onset Alzheimer's disease [3].

In conclusion, Tmcc2 is essential for normal erythropoiesis and auditory hair cell function. Gene knockout models in mice and Drosophila have revealed its role in these processes and in neurodegenerative-like conditions. Understanding Tmcc2 provides insights into the mechanisms of anemia, hearing loss, and neurodegenerative diseases [1,2,3].