This deliverable presents the updated version of Deliverable 2.1 “Ethical Guidelines, Data Collection and Sharing” and provides an updated overview of the legal, ethical, regulatory, and data governance framework applicable to the HEREDITARY project. Since the submission of D2.1 in June 2024, several important developments have occurred, including the implementation of Regulation (EU) 2024/1689 (AI Act), the evolution of the European Health Data Space (EHDS), increasing cybersecurity requirements associated with the NIS2 Directive, and the operational development of semantic, FAIRification, and federated discovery infrastructures within HEREDITARY. The deliverable reviews these developments and assesses their implications for multimodal health data processing, secondary use of health data, distributed data discovery, privacy-preserving analytics, and AI governance. In addition, the document reports updates concerning ethical approvals, data management, and governance procedures across consortium partners, including the role of the Data Management Plan, FAIRification activities, the HEREDITARY Ontology (HERO), and Hereditary Data Network (HDN). It also introduces a prospective Optical Coherence Tomography (OCT) cohort of Amyotrophic Lateral Sclerosis (ALS) patients at the University of Turin, currently in the preparatory and ethics approval phase. Once approved, the cohort will support future multimodal and multicenter analyses involving ALS, Parkinson’s disease, and Multiple Sclerosis datasets available within the consortium. Overall, D2.2 confirms the continued alignment of HEREDITARY with applicable European and national legal, ethical, and regulatory requirements while supporting privacy-preserving, trustworthy, and responsible health data research.