This study demonstrated that HFD-induced obesity leads to increased circulating insulin levels and worsens the preeclampsia-like phenotypes in pregnant mice lacking ASB4, as evidenced by HFD-Asb4−/− dams having a higher BP and urinary albumin excretion, more severe kidney impairment, and worse pregnant outcomes than NC-Asb4−/− dams. Here, ASB4 is linked to preeclampsia.