TMEM114 (transmembrane protein 114) is a novel four-exon gene located on chromosome 16.3 that encodes a 223-amino acid transmembrane protein with four predicted transmembrane domains 1. The protein is structurally related to voltage-dependent calcium channel gamma subunit family members rather than claudins, and contains N-linked glycosylation sites 2. In the eye, TMEM114 is expressed in lens epithelial cells and the transitional zone of early fiber differentiation 1, where it plays a role in normal eye development 2. TMEM114 is clinically significant for ocular development and metabolism. Loss-of-function mutations cause autosomal dominant congenital cataracts, with missense mutations (p.I35T, p.F106L) affecting highly-conserved amino acids in the first extracellular domain 1. Promoter disruption via chr16 translocation t(16;22) also causes familial lamellar cataract 1. Beyond ophthalmology, genome-wide association studies identified a TMEM114 SNP (rs62018863) associated with preserved ratio impaired spirometry (PRISm), a novel lung function phenotype, suggesting involvement in respiratory health 3. Pharmacogenetic studies implicate TMEM114 polymorphisms in incretin pathway disturbances affecting glycemic response and weight loss to GLP-1 receptor agonist therapy in type 2 diabetes 45, with variants showing 30-40% effects on GLP-1-stimulated insulin secretion 5.