This article presents an in-depth analysis of selected CASP16 targets, with a focus on their biological and functional significance. The authors highlight the most relevant features of the target proteins and discuss how well these were reproduced in the submitted predictions. While the overall performance of structure prediction methods remains impressive, challenges persist, particularly in modeling rare structural motifs, flexible regions, small molecule interactions, post-translational modifications, and biologically important interfaces. Addressing these limitations can strengthen the role of structure prediction in complementing experimental efforts and advancing both basic research and biomedical applications.