This review summarizes evidence on IL-4’s biological properties, its canonical (Janus kinase [JAK]–signal transducer and activator of transcription 6 [STAT6]) and non-canonical (insulin receptor substrate [IRS]–phosphoinositide 3-kinase [PI3K]–protein kinase B [AKT]) signaling pathways, and its roles in renal diseases (including AKI, lupus nephritis, diabetic nephropathy, and other chronic glomerulopathies). The gene discussed is IARS1; the disease is lupus nephritis.