Chugh et al. (2014) describe, in detail, the discovery of angiopoietin-like protein 4 (ANGPTL4), secreted by podocytes, as a major player in human nephrotic syndrome and highlight the strategy used to identify and then selectively investigate genes and proteins that lay at the intersection of proteinuria, hyperlipidemia, and edema during disease progression. Here, ANGPTL4 is linked to hyperlipidemia.