TMEM14C is a transmembrane protein essential for mitochondrial heme biosynthesis in erythroid cells 1. The protein functions as part of the mitochondrial heme metabolism pathway, with disruption causing increased susceptibility to artemisinin compounds in parasites 2. TMEM14C is critically regulated by RNA splicing mechanisms, particularly through the spliceosome component SF3B1. Mutations in SF3B1, commonly found in myelodysplastic syndromes (MDS), cause aberrant splicing of TMEM14C transcripts, which directly contributes to the formation of ring sideroblasts - a hallmark feature of SF3B1-mutant MDS 345. The E592K variant of SF3B1 preserves normal TMEM14C splicing and associates with MDS lacking ring sideroblasts, demonstrating the direct relationship between TMEM14C splicing and disease phenotype 3. However, studies in mouse models show that while Sf3b1 mutations cause anemia, the murine ortholog Tmem14c is not aberrantly spliced, suggesting species-specific differences in splicing regulation 6. TMEM14C has also been identified as a prognostic marker in head and neck squamous cell carcinoma, where its expression correlates with patient survival outcomes 7.