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Here, we report the genome mining results of 18,082 extremophilic microorganisms, combined with structural modelling, enzyme\u2013substrate simulations and experimental validation, which enables the identification of PET\u2010active true lipases. Two true lipases, Lip\n                    <jats:sub>Bv<\/jats:sub>\n                    and Lip\n                    <jats:sub>Sh1<\/jats:sub>\n                    , hydrolyse PET substrates and homologous enzymes within their respective clusters also retain PET\u2010hydrolysing activity, supporting the existence of specific lipase lineages associated with PET hydrolysis. Structural analyses suggest that differences in loop organization and active\u2010site accessibility may contribute to the observed PET\u2010hydrolysing activity and hydrolysis product profiles. These lipase lineages clustered separately from 1322 putative PETase homologues from the same extremophile genomes, while all groups remained distinct from previously characterized PETases. These findings expand the evolutionary diversity of PET\u2010hydrolysing enzymes in extremophiles.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.70432","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T06:30:39Z","timestamp":1787380239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2010Guided Extremophile Genome Mining Expands the\n                    <scp>PETase<\/scp>\n                    Landscape and Reveals\n                    <scp>PET<\/scp>\n                    \u2010Hydrolysing True Lipase Lineages"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4380-4888","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Mu\u00f1oz\u2010Tafalla","sequence":"first","affiliation":[{"name":"PhD Program in Biotecnology, Faculty of Pharmacy and Food Sciences Universitat de Barcelona (UB)  Barcelona 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