Though HCAR1 signaling via cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) has been observed in adipocytes and neuronal cells [24,25], and HCAR1 was shown to mediate macrophage and monocyte inflammatory response via arrestin β-2, toll-like receptor 4 (TLR4), and NLRP3 inflammasome [26,27], lactate-stimulated HCAR1 signaling in cancer cells is poorly understood. The gene discussed is TLR4; the disease is cancer.