Here, we identified a pediatric-onset SLE patient with germline mutations in both ACP5 and SAMHD1.This patient carried three novel mutations from both father and mother, resulting in a double missense mutation in ACP5 (c.1152G>T in the mother and c.420G>A in the father) and a single missense mutation in SAMHD1 (c.1423G>A in the mother). This evidence concerns the gene ACP5 and systemic lupus erythematosus.