NAAA (N-acylethanolamine acid amidase) is a lysosomal cysteine hydrolase that degrades bioactive fatty acid amides, with the highest activity toward palmitoylethanolamide (PEA) followed by other N-acylethanolamines 1. The enzyme exhibits optimal catalytic activity at acidic pH (4.5-5.0), consistent with its lysosomal localization 1. NAAA is highly expressed in immune tissues including lung, spleen, thymus, and particularly in alveolar macrophages 1. Mechanistically, NAAA controls inflammation by hydrolyzing PEA, an anti-inflammatory PPAR-α agonist, thereby regulating PPAR-α signaling pathways 2. This regulation appears critical for both induction and resolution of inflammatory responses 2. NAAA demonstrates significant disease relevance across multiple pathological conditions. In inflammatory bowel disease, increased NAAA expression correlates with intestinal fibrosis, and NAAA inhibition reduces fibrosis through modulation of macrophage activity and IL-23 signaling 3. In pain chr4, NAAA activation in monocytes enables hyperalgesic priming through suppression of PPAR-α signaling 4. Additionally, NAAA contributes to neurodegeneration, with elevated expression observed in Parkinson's disease patients and mouse models, where NAAA inhibition protects dopamine neurons 5. These findings establish NAAA as a promising therapeutic target for anti-inflammatory and neuroprotective interventions.