This study provides new mechanistic insights into the inhibitory effects of the neurosteroid 3α,5α-THP on TLR4 signaling, potentially opening new avenues for modulating neuroimmune responses in conditions characterized by chronic inflammation, such as alcohol use disorder, depression, and neurodegenerative diseases [1,2,3,4,5,6,7,8,9,10,11,12]. Here, TLR4 is linked to major depressive disorder.