Ferroptosis suppressor protein 1 (FSP1) has emerged as a critical regulator of ferroptosis, an iron-dependent form of programmed cell death with significant therapeutic potential in cancer treatment. Despite rapidly expanding research, current knowledge on FSP1 remains fragmented across various tumor types and experimental contexts. The aim of this review is to systematically integrate the latest evidence regarding the molecular structure, biological functions, and regulatory mechanisms controlling FSP1 expression, emphasizing its involvement in tumor progression and resistance to therapy. Readers can expect comprehensive coverage of FSP1’s structural characteristics, enzymatic roles, transcriptional and post-transcriptional regulation, and its pathological significance in hepatocellular carcinoma, colorectal cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, and leukemia. We further evaluate emerging therapeutic strategies targeting FSP1 aimed at overcoming resistance and improving clinical outcomes. Relevant studies were systematically identified by searching PubMed, Web of Science, and Embase databases, focusing particularly on the recent and impactful literature to guide future research directions.

Gallbladder diseases spanning cholelithiasis, cholecystitis, and gallbladder cancer represent a clinically heterogeneous continuum in which type 2 diabetes mellitus (T2DM) acts as a key metabolic modifier. Conventional models centered on bile supersaturation alone do not sufficiently account for the persistent inflammation and inter-individual variability frequently observed in practice. Here, we synthesize emerging evidence implicating the gut microbiota–bile acid (BA) axis as an integrative mechanism linking metabolic dysregulation, barrier dysfunction, and biliary pathobiology in the diabetic host. Hyperglycemia and insulin resistance, together with impaired mucosal resilience, are associated with shifts in microbial community structure and BA-transforming functions (e.g., bile salt hydrolase and 7α-dehydroxylation), favoring a more hydrophobic BA pool. These changes may disrupt BA receptor signaling, including FXR–FGF15/19 and TGR5-related pathways, thereby amplifying metabolic inflammation, promoting lithogenic bile formation, and impairing gallbladder motility. In parallel, barrier vulnerability may facilitate microbial translocation and LPS-driven immune activation, reinforcing a feed-forward loop that supports the gallstone–inflammation–carcinogenesis trajectory. Translationally, microbiome- and BA-oriented strategies (dietary patterns, bile acid therapeutics, and targeted microbiome modulation) are promising adjuncts, yet precision management should explicitly consider medication- and weight loss–related confounding—particularly with incretin-based therapies—to optimize biliary outcomes across disease stages.