ANXA11 (Annexin A11) is a calcium-dependent phospholipid-binding protein with critical roles in neuronal function and disease pathogenesis 1. Mechanistically, ANXA11 functions as a molecular tether linking RNA granules to lysosomes via its N-terminal low complexity domain and C-terminal membrane-binding domain, enabling long-distance RNA transport essential for neuronal protein synthesis 2. This transport function is critical for maintaining proper spatial organization in polarized neurons. ANXA11 has emerged as a central player in neurodegenerative diseases, particularly through its interactions with TDP-43. In frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) type C, ANXA11 co-assembles with TDP-43 into unprecedented heteromeric amyloid filaments, with ANXA11 existing primarily as an N-terminal fragment 3. Pathogenic ANXA11 variants impair lysosomal-RNA granule trafficking and promote TDP-43 mislocalization, contributing to amyotrophic lateral sclerosis and corticobasal syndrome 24. ANXA11 aggregates appear in all FTLD-TDP type C cases and in smaller proportions of sporadic ALS and other TDP-43 proteinopathies 5. Beyond neurodegeneration, ANXA11 genetic variants modulate susceptibility to sarcoidosis and other immune-mediated diseases, with protective effects associated with specific alleles 67. These findings establish ANXA11 as a multifunctional regulator linking neuronal RNA transport, protein aggregation pathology, and immune function.