Slc4a11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH [1]. Although it doesn't transport bicarbonate, it shares properties with other SLC4 family members. It plays a role in multiple biological processes, with its expression induced by oxidative stress via the transcription factor NRF2.

In Slc4a11 knockout (KO) mice, phenotypes such as corneal endothelial dystrophy and hearing deficits are observed, mirroring the conditions in humans with SLC4A11 mutations [1,2]. The inducible Slc4a11 KO mouse model shows that loss of Slc4a11 leads to corneal edema through perturbation of the corneal endothelial pump, accompanied by mitochondrial superoxide-induced Src kinase activation, disruption of tight junctions, and changes in lactate transporters and Na-K ATPase activity [4,5]. In hepatocellular carcinoma, SLC4A11 mediates ammonia import, promoting cancer stemness [3].

In conclusion, Slc4a11 is crucial for maintaining normal physiological functions, especially in the corneal endothelium, inner ear, and metabolism-related processes. The Slc4a11 KO and inducible KO mouse models have been instrumental in revealing its role in diseases like corneal endothelial dystrophy and in understanding its contribution to cancer stemness in hepatocellular carcinoma.