CA4 (carbonic anhydrase 4) is a membrane-associated enzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate and protons, playing a crucial role in pH homeostasis 1. The enzyme is essential for maintaining both intracellular and extracellular pH balance and may stimulate sodium/bicarbonate transporter activity of SLC4A4 in pH regulation 1. CA4 demonstrates particular importance in ocular physiology, where it is essential for acid overload removal from the retina and retinal epithelium, as well as acid release in the choriocapillaris of the choroid 1. The protein localizes to various cellular compartments including plasma membranes, transport vesicles, and secretory granules, with specific enrichment at apical and basolateral surfaces. Clinically, CA4 is associated with retinitis pigmentosa 17, indicating its critical role in retinal function. Beyond its primary enzymatic function, CA4 has emerged as a biomarker in various pathological conditions. In parathyroid carcinoma, CA4 shows differential nuclear expression compared to adenomas, with significantly lower nuclear percentage serving as a potential diagnostic marker 2. The enzyme's expression patterns also show relevance in neurodegenerative diseases, with spatial transcriptomic studies revealing region-specific alterations in Alzheimer's disease hippocampal regions 3.