Two forms of intercalated cells are present in kidney collecting tubules, the ␣ cell has apical endocytosis, apical H ϩ -ATPase and basolateral band 3, while  cells have reversed polarity of these proteins and no apical endocytosis. When a  cell line was seeded at high density, it changed into the ␣ form. We previously showed that a partially purified 230 kD extracellular matrix protein of high density cells was able to retarget band 3 from apical to basolateral domains and stimulated apical endocytosis in vitro (Van Adelsberg, J., J.C. Edwards, J. Takito, B. Kiss, and Q. Al-Awqati. 1994. Cell. 76:1053-1061). We now purify this protein, which was named hensin, to near homogeneity and find that it belongs to the macrophage scavenger receptor cysteine rich (SRCR) family. An antibody, generated against a fusion protein made from a partial cDNA recognized a 230-kD protein in rabbit kidney and in the intercalated cell line.