The platelet-derived growth factor (PDGF) family consists of four disulfide-linked homodimers and one heterodimer (PDGF-AB). These proteins regulate diverse cellular functions through interactions with PDGF Ra and Rb. Mature PDGF-DD associates with PDGF Rb and triggers signaling through PDGF Rb homodimers and PDGF Ra/b heterodimers. The human PDGF-DD cDNA encodes a 370aa precursor that includes a 23aa signal sequence, one CUB domain, and one PDGF/VEGF domain. The PDGF/VEGF domain shares 27-35aa sequence identity with the corresponding regions of other PDGF family members. Human PDGF-DD shares 87aa sequence identity with mouse and rat PDGF-DD. PDGF-DD is secreted as a100kD latent homodimer which is activated by proteolysis to release a 35kD bioactive protein containing the PDGF/VEGF homology domain. A splice variant of PDGF-DD has a 6aa deletion near the N-terminus. A 72aa deletion within the PDGF/VEGF domain generates an inactive protein in mouse but has not been detected in human. PDGF-DD is widely expressed in embryonic and adult tissues, and PDGF Rb is expressed in a generally complementary pattern. PDGF-DD functions as a growth factor for renal artery smooth muscle cells and lens epithelial cells, and as a macrophage chemoattractant. PDGF-DD is overexpressed in and contributes to several disease states, including renal and hepatic fibrosis, mesangial proliferative glomerulopathy, pulmonary lymphoid infiltration, and many cancers. PDGF-DD functions in both paracrine and autocrine manners.