Solute carrier family 12 member 8 (SLC12A8)

Solute carrier family 12 member 8 (SLC12A8) is a membrane protein encoded by the SLC12A8 gene on human chromosome 3[1][3]. It belongs to the broader SLC12 family of cation-chloride cotransporters, but recent findings define it as the first NMN transporter in mammals, critical for cellular NAD⁺ metabolism, especially in the intestine and in the context of aging[2][4]. Unlike classical SLC12A family members, SLC12A8 is sodium-dependent and specific for NMN, not for nicotinamide riboside or structurally related metabolites[2]. The gene is a candidate for psoriasis susceptibility, may impact keratinocyte biology, and its upregulation in the aged intestine is thought to counteract age-related declines in NAD⁺[2][5]. Currently, no approved drugs specifically target SLC12A8, but it is experimentally accessible using NAD⁺ metabolism modulators. Deficiency or loss of SLC12A8 function reduces NMN uptake and tissue NAD⁺ levels, with potential ramifications for health and age-associated decline[2][5].

Other names

SLC12A8CCC9Cation-chloride cotransporter 9Solute carrier family 12 member 8

Sodium-dependent transmembrane transport of NMN (facilitates direct uptake, distinguishing SLC12A8 from other family members that use chloride and potassium). Upregulation in response to NAD⁺ decline allows rapid replenishment of NAD⁺ via NMN. Modulation of keratinocyte proliferation (possible ATPase-coupled transport).