We report the first confirmed case of high pathogenicity avian influenza virus (HPAIV) infection in a peregrine falcon (Falco peregrinus) on Amami-Oshima Island, a region known for its unique biodiversity. The isolate, A/peregrine falcon/Kagoshima/5704A001/2025 (H5N2), showed genetic and phylogenetic divergence across all eight gene segments. Specific amino acids in the PA protein associated with increased pathogenicity in birds and mammals were also identified. Despite global surveillance, related ancestral viruses remain unreported. These findings highlight the need for expanded geographic surveillance and timely, transparent data sharing to better track and respond to emerging HPAIV threats.