In hypoosmotic medium, skate erythrocytes swell then lose taurine and other solutes with obligate water to achieve a regulatory volume decrease (RVD), occuring over 90 min. The skate erythrocyte anion exchanger isoform 1 (skAE1) participates in the RVD and increased surface expression after hypoosmotic-induced volume expansion occurs within 5 min, but decreases to baseline within 120 min. The subsequent fate of skAE1 was the focus of these studies. SkAE1 sent to the surface becomes monoubiquitinated, a modification present while skAE1 is associated with clathrin and rab5 but which is removed before skAE1 is passed to the rab4 compartment. SkAE1 endocytosis involves clathrin-mediated internalization. Surface plasma membrane skAE1 forms tetramers and demonstrates increased tyrosine phosphorylation, both of these alterations decreasing before skAE1 appearance in the rab5 compartment. Volume expansion-stimulated surface skAE1 comes from an intracellular pool in a buoyant membrane fraction resistant to non-ionic detergent extraction (DRM) and the amount of skAE1 increases in this buoyant DRM fraction in the surface. Clathrin heavy chain is found largely in the erythrocyte DRM, but in dense rather than buoyant fractions. Rab5 and rab4 containing membranes are largely detergent soluble, suggesting that as skAE1 is passed to clathrin and then to rab5 compartments, the membrane microdomain composition changes. The present studies demonstrate that skAE1 which appears on the surface after hypoosmotic-induced volume expansion is monoubiquitinated that may serve as a signal for surface removal. This modification is removed after clathrin-mediated removal in a membrane domain containing rab5, potentially permitting recycling and reuse of skAE1.