The IPD-IMGT/HLA Database, established in 1998, has evolved over 25 years to serve as a critical resource for HLA allele sequences. Initially developed as a simple multiple sequence alignment, it has grown to include over 38,000 HLA alleles for 40 genes and 901 alleles for five related genes. The database has adapted to technological advancements, including next-generation sequencing (NGS), which has significantly increased the volume and complexity of sequences. The database now supports a wide range of users, including researchers, clinicians, and commercial entities, and provides high-quality, curated data essential for HLA research and clinical applications. The database's success is attributed to its ability to maintain high standards of curation and adapt to new technologies. It has expanded beyond HLA to include other gene systems, such as IPD-KIR, IPD-NHKIR, and IPD-MHC. The database has also evolved its tools and infrastructure to handle increasing data volumes and user demands. The IPD-IMGT/HLA Database now offers APIs for programmatic access, enabling integration with third-party software and facilitating large-scale data analysis. The database has been instrumental in tracking HLA sequence variation, including intronic and UTR variants, which have become more prevalent with the adoption of NGS. The database's ability to manage highly variable sequences and provide accurate, curated data is crucial for understanding HLA polymorphism and its implications in transplantation and disease. The database continues to evolve to meet the challenges of increasing data volumes and the need for more sophisticated analysis tools, including the potential integration of artificial intelligence for future developments. The IPD-IMGT/HLA Database remains a vital resource for HLA research and clinical applications, adapting to new technologies and user needs to ensure its continued relevance and utility.The IPD-IMGT/HLA Database, established in 1998, has evolved over 25 years to serve as a critical resource for HLA allele sequences. Initially developed as a simple multiple sequence alignment, it has grown to include over 38,000 HLA alleles for 40 genes and 901 alleles for five related genes. The database has adapted to technological advancements, including next-generation sequencing (NGS), which has significantly increased the volume and complexity of sequences. The database now supports a wide range of users, including researchers, clinicians, and commercial entities, and provides high-quality, curated data essential for HLA research and clinical applications. The database's success is attributed to its ability to maintain high standards of curation and adapt to new technologies. It has expanded beyond HLA to include other gene systems, such as IPD-KIR, IPD-NHKIR, and IPD-MHC. The database has also evolved its tools and infrastructure to handle increasing data volumes and user demands. The IPD-IMGT/HLA Database now offers APIs for programmatic access, enabling integration with third-party software and facilitating large-scale data analysis. The database has been instrumental in tracking HLA sequence variation, including intronic and UTR variants, which have become more prevalent with the adoption of NGS. The database's ability to manage highly variable sequences and provide accurate, curated data is crucial for understanding HLA polymorphism and its implications in transplantation and disease. The database continues to evolve to meet the challenges of increasing data volumes and the need for more sophisticated analysis tools, including the potential integration of artificial intelligence for future developments. The IPD-IMGT/HLA Database remains a vital resource for HLA research and clinical applications, adapting to new technologies and user needs to ensure its continued relevance and utility.