Model of ion transport pathways of the human erythrocyte. Ion transport pathways of the human erythrocyte are shown. Gradient-driven transport pathways include AE1: the anion exchange protein 1, band 3, encoded by SLC4A1; NKCC1 encoding Na-K-Cl cotransporter 1; KCC: K-Cl cotransporters of the family of chloride-cation cotransporters; VDAC: voltage-dependent anion channels; NHE1 encoding the sodium/hydrogen exchanger 1; and VRAC: voltage-regulated anion channels, encoded in part by SWELL1 (LRRC8A). Gradient-driven leak pathways, not otherwise identified and indicated by the arrows, also exist in mature erythrocytes. PIEZO1 is a mechano-activated channel of the erythrocyte membrane. Other erythrocyte membrane channels are the aquaporins, water channels encoded by AQP1 and AQP3, and KCNN4 encoding the Gardos channel, a calcium-activated potassium channel. Active transporters are the calcium ATPase, encoded by ATP2B4, and sodium-potassium ATPase, the multicomponent sodium pump composed of α1 and α3 isoforms, β1, β2, and β3 isoforms, and the γ modulator. NMDAR, the multicomponent N-methyl d-aspartate receptor participating in calcium regulation in erythroid cells, is also shown. Other transport pathways (eg, CO₂, amino acids, glucose, urea, etc) are not shown.