SGPL1 and nephrotic syndrome: Since it was previously reported that systemic SPL knockout mice show increased plasma levels of the proinflammatory cytokine, IL-6 [32], this also fosters an alternative hypothesis that the nephrotic syndrome seen in Sgpl1−/− (SPL knockout) mice and in Sgpl1 mutant patients is mediated by a plasma factor and not necessarily by a podocyte-specific mechanism.