Kirrel1

Kin of IRRE-like protein 1 (KIRREL1) is also known as NEPH1, is type I transmembrane glycoproteina that belongs to the nephrin-like protein family, which includes NEPH2 and NEPH3 (KIRREL2). The cytoplasmic domains of these proteins interact with the C terminus of podocin (NPHS2). KIRREL1 is expressed in filtration slits of kidney podocytes, cells involved in ensuring size- and charge-selective ultrafiltration of blood. KIRREL1 forms cis hetero­oligomers with nephrin, which brings together signaling molecules that direct actin polymerization. This interaction is essential for barrier function in the slit diaphragm, and mice deleted for KIRREL1 die perinatally due to proteinuria and failure to thrive. KIRREL1 is crucial for the integrity of the slit diaphragm, as KIRREL gene knockout mice results in effacement of glomerular podocytes, heavy proteinuria, and early postnatal death.