Mutations of NPHS1 or NPHS2, the genes encoding for the glomerular podocyte proteins nephrin and podocin, cause steroid‐resistant proteinuria. In addition, mice lacking NEPH1 develop a nephrotic syndrome that resembles NPHS mutations, suggesting that all three proteins are essential for the integrity of glomerular podocytes. Podocin interacts with the C‐terminal domain of nephrin and facilitates nephrin‐dependent signaling. NEPH1, a member of the immunoglobulin superfamily, is structurally related to nephrin. We report now that NEPH1 belongs to a family of three closely related proteins that interact with the C‐terminal domain of podocin. All three NEPH proteins share a conserved podocin‐binding motif; mutation of a centrally located tyrosine residue dramatically lowers the affinity of NEPH1 for podocin. NEPH1 triggers AP‐1 activation similarly to nephrin but requires the presence of Tec family kinases for efficient transactivation. We conclude that NEPH1 defines a new family of podocinbinding molecules that are potential candidates for hereditary nephrotic syndromes not linked to either NPHS1 or NPHS2.