The Universal Protein Resource (UniProt) is a comprehensive, high-quality, and freely accessible resource for protein sequences and functional annotations. It integrates, interprets, and standardizes data from various sources to provide the most extensive catalog of protein information. The UniProt Consortium, comprising groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB), and the Protein Information Resource (PIR), updates and distributes UniProt every 4 weeks. UniProt's databases include the UniProt Knowledgebase (UniProtKB), which is expertly curated and consists of a reviewed section (UniProtKB/SwissProt) and an unreviewed section (UniProtKB/TrEMBL). The UniProt Archive (UniParc) serves as a comprehensive sequence repository, while the UniProt Reference Clusters (UniRef) merge closely related sequences for better sequence similarity searches. The UniProt Metagenomic and Environmental Sequence (UniMES) database caters to the growing field of metagenomics. UniProt's biocuration process involves manual and automatic annotation, with a focus on high-quality, standardized information. Manual curation ensures that experimental data from literature are accurately integrated, while automatic annotation systems like UniRule and SAAS handle uncharacterized protein sequences. The Gene Ontology (GO) annotation project enhances the biological context of UniProtKB records, and the UniProt genomic pipeline links UniProtKB to genomic resources for variant analysis and disease annotation. UniProt continues to grow, addressing the challenges of the complete genome era by developing complete and reference proteomes. The UniProt Web site has been redesigned for improved usability, and extensive cross-references and ID mapping services are provided to facilitate data integration. The resource is freely available for both commercial and non-commercial use, with new releases published every 4 weeks.The Universal Protein Resource (UniProt) is a comprehensive, high-quality, and freely accessible resource for protein sequences and functional annotations. It integrates, interprets, and standardizes data from various sources to provide the most extensive catalog of protein information. The UniProt Consortium, comprising groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB), and the Protein Information Resource (PIR), updates and distributes UniProt every 4 weeks. UniProt's databases include the UniProt Knowledgebase (UniProtKB), which is expertly curated and consists of a reviewed section (UniProtKB/SwissProt) and an unreviewed section (UniProtKB/TrEMBL). The UniProt Archive (UniParc) serves as a comprehensive sequence repository, while the UniProt Reference Clusters (UniRef) merge closely related sequences for better sequence similarity searches. The UniProt Metagenomic and Environmental Sequence (UniMES) database caters to the growing field of metagenomics. UniProt's biocuration process involves manual and automatic annotation, with a focus on high-quality, standardized information. Manual curation ensures that experimental data from literature are accurately integrated, while automatic annotation systems like UniRule and SAAS handle uncharacterized protein sequences. The Gene Ontology (GO) annotation project enhances the biological context of UniProtKB records, and the UniProt genomic pipeline links UniProtKB to genomic resources for variant analysis and disease annotation. UniProt continues to grow, addressing the challenges of the complete genome era by developing complete and reference proteomes. The UniProt Web site has been redesigned for improved usability, and extensive cross-references and ID mapping services are provided to facilitate data integration. The resource is freely available for both commercial and non-commercial use, with new releases published every 4 weeks.