TMEM237, previously known as ALS2CR4, is a gene with diverse functions. It localizes to the ciliary transition zone, playing a crucial role in ciliogenesis and regulation of Wnt signaling. It is also involved in multiple biological processes such as lactate transport in photoreceptor outer segment plasma membrane, and may be related to riboflavin uptake in the intestine [2,3,4].

Mutations in TMEM237 have been associated with Joubert syndrome related disorders. Loss of mammalian TMEM237 leads to defective ciliogenesis and deregulation of Wnt signaling. Disrupting Danio rerio (zebrafish) tmem237 expression causes gastrulation defects consistent with ciliary dysfunction, and in Caenorhabditis elegans, jbts-14 (homolog of TMEM237) genetically interacts with nphp-4 to control basal body-TZ anchoring and ciliogenesis [3]. In hepatocellular carcinoma, HIF-1α-activated TMEM237 promotes cancer progression via the NPHP1/Pyk2/ERK pathway. TMEM237 interacts with NPHP1, strengthens the interaction between NPHP1 and Pyk2, triggering the phosphorylation of Pyk2 and ERK1/2, thus facilitating the proliferation, migration, invasion, and EMT of HCC cells and promoting tumor growth and metastasis in mice [1].

In conclusion, TMEM237 is essential for ciliogenesis, Wnt signaling regulation, and normal physiological functions in various tissues. Its malfunction, as revealed through gene-knockout-like models in different organisms, is closely related to Joubert syndrome related disorders and hepatocellular carcinoma progression, highlighting its significance in understanding the mechanisms of these diseases.