TLR4 up‐regulation has the potential to enhance TLR4/NF‐κB signaling and further worsen cardiac hypertrophy and fibrosis.[56] Our previous report has verified an inhibitory role of MANF in TLR4/NF‐κB activation via MANF‐S100A8 interaction,[18] indicating another possible channel for cardiomyocyte MANF to protect against MH through TLR4 suppression. The gene discussed is S100A8; the disease is cardiac hypertrophy.