SLC12A4 encodes potassium-chloride cotransporter 1 (KCC1), a ubiquitously expressed electroneutral transporter essential for cellular fluid and ion homeostasis 1. KCC1 mediates K+-Cl- cotransport across plasma membranes and lysosomal membranes, functioning in cell volume regulation and maintaining potassium and chloride ion balance 1. The SLC12A4 promoter lacks a TATA box but contains an initiator element and downstream promoter element regulated by AP-2 and Sp1 transcription factors 2. In erythrocytes, KCC1 contributes significantly to K-Cl cotransport and has been proposed as a modifier gene in sickle cell disease, where elevated K-Cl cotransport occurs 2. KCC1 participates in a chloride-sensing signaling pathway involving WNK1-OSR1-SPAK kinases that controls phagocyte responses during apoptotic cell clearance; loss of SLC12A4 inhibits corpse uptake and anti-inflammatory responses 3. The first disease-associated KCC1 variant (E1065K) reduces cotransporter functional activation under hypotonic conditions, suggesting a role in osmotic regulation 4. SLC12A4 is co-expressed with SLC12A2 in multiple tissues and serves as a therapeutic target; inhibition of both transporters reduces inflammation and angiogenesis in diabetic retinopathy 5. Altered SLC12A4 expression associates with papillary thyroid carcinoma recurrence 6.