This hypothesis is confirmed by direct and sialylation-dependent CD24-Siglec E interaction, requirement of CD24 in either the same (cis) or separate cells (trans) in constitutional activation of Siglec E. More importantly, in a Siglec E-dependent manner, CD24Fc effectively suppressed obesity, dyslipidemia, insulin resistance, and NASH in multiple mouse models. The gene discussed is CD24; the disease is metabolic dysfunction-associated steatohepatitis.