{
 "gene": "ACSL4",
 "run_date": "2026-06-09T22:02:39",
 "timeline": {
  "current_model": "ACSL4 is a long-chain acyl-CoA synthetase with substrate preference for polyunsaturated fatty acids (especially arachidonic and adrenic acids) that acts as a critical pro-ferroptotic enzyme by esterifying PUFAs into membrane phospholipids, providing the peroxidation substrates required for ferroptosis execution; its activity and stability are tightly regulated by multiple post-translational modifications\u2014including phosphorylation by PKC\u03b2II (activating) and CDK1 (triggering UBR5-mediated ubiquitin degradation), SUMOylation by TRIM28 at K532 (stabilizing), acetylation by HAT1 at K383 (stabilizing, blocking FBXO10-mediated degradation), lactylation at K412, m6A-dependent mRNA stabilization via METTL3/YTHDC1, and autophagic degradation via HSC70/CMA or OPTN-selective autophagy\u2014while its transcription is driven by SP1, Sp1, STAT1/IRF1, STAT3, E2F (downstream of RB1), EGR1 (downstream of YAP), and NFIL3, and inhibited by HIF-1\u03b1; beyond ferroptosis, ACSL4 promotes tumor metastasis by remodeling membrane phospholipid composition to activate integrin \u03b21 signaling and enhance membrane fluidity, reprograms lipid metabolism through the c-Myc/SREBP1 axis and FAO-dependent histone acetylation, regulates neuroinflammation via VGLL4/NF-\u03baB, and interacts directly with partner proteins including STING, FUNDC1, and MMD/MBOAT7 to modulate disease-specific lipid peroxidation pathways."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0016874",
     "term_label": "ligase activity",
     "supporting_discovery_ids": [
      2,
      3,
      4,
      5
     ]
    },
    {
     "term_id": "GO:0016740",
     "term_label": "transferase activity",
     "supporting_discovery_ids": [
      0,
      2,
      26
     ]
    },
    {
     "term_id": "GO:0008289",
     "term_label": "lipid binding",
     "supporting_discovery_ids": [
      0,
      8,
      28
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005739",
     "term_label": "mitochondrion",
     "supporting_discovery_ids": [
      39,
      40,
      32
     ]
    },
    {
     "term_id": "GO:0005886",
     "term_label": "plasma membrane",
     "supporting_discovery_ids": [
      28,
      29
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-5357801",
     "term_label": "Programmed Cell Death",
     "supporting_discovery_ids": [
      0,
      6,
      19
     ]
    },
    {
     "term_id": "R-HSA-1430728",
     "term_label": "Metabolism",
     "supporting_discovery_ids": [
      2,
      31,
      30
     ]
    },
    {
     "term_id": "R-HSA-1643685",
     "term_label": "Disease",
     "supporting_discovery_ids": [
      4,
      43,
      27
     ]
    }
   ],
   "complexes": [],
   "partners": [
    "MBOAT7",
    "MMD",
    "STING",
    "FUNDC1",
    "UBR5",
    "RNF25",
    "TRIM28",
    "FBXO10"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "O60488",
   "full_name": "Long-chain-fatty-acid--CoA ligase 4"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 7,
  "faith_total": 7,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.270564
 }
}