{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeuronal apoptosis inhibitory protein (NAIP) is a multifunctional protein best known for its role in innate immunity. NAIP acts as a cytosolic sensor that detects bacterial virulence factors—including type III secretion system needle proteins and flagellin—thereby nucleating the assembly of the NLRC4 inflammasome complex. This activation triggers caspase‐1–dependent cellular responses that promote inflammatory cytokine release and pyroptosis, a process fundamental to host defense against diverse pathogens such as Salmonella, Shigella, and Legionella. In addition, NAIP gene dosage can modulate the amplitude of this response, suggesting that higher NAIP levels may intensify inflammasome-dependent cell death upon pathogen encounter."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immune-sensing role, NAIP exerts significant antiapoptotic activity. Its unique structure—which integrates baculoviral inhibitory repeat (BIR), nucleotide-binding oligomerization (NOD), and leucine-rich repeat (LRR) domains—enables NAIP to interact with and inhibit caspase-9 during apoptosome assembly in an ATP-dependent manner. This property prevents premature or excessive activation of the intrinsic apoptosis pathway and safeguards cell viability. Moreover, NAIP expression is governed by a complex transcriptional architecture, including multiple distinct promoters and the exaptation of endogenous retroviral long terminal repeats (LTRs) and Alu elements, further underscoring its finely tuned regulatory control."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNAIP’s multifunctionality is also evident in its impact on disease modulation, particularly in neurodegenerative and neuromuscular contexts. In spinal muscular atrophy (SMA), for example, deletion or reduced copy number of the NAIP gene correlates with increased disease severity and earlier onset, highlighting its role as a modifier of neuronal survival. Differential NAIP expression in both neuronal and non-neuronal cells further influences susceptibility to apoptosis in diverse tissues. Intriguingly, emerging data also implicate NAIP in nonapoptotic processes such as cytokinesis, suggesting additional cellular functions that may contribute to tissue homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jieling Yang, Yue Zhao, Jianjin Shi, et al. 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