Objective:

To explore the role of Annexin A11 (ANXA11) in neurodegenerative diseases, particularly in relation to TDP-43 pathology in frontotemporal degeneration (FTD).

Approach:

• Introduction to ANXA11: Discusses the structural features and physiological roles of ANXA11, including its involvement in calcium signaling, RNA transport, and membrane trafficking.
• ANXA11 Structure: Describes the structural characteristics of ANXA11, including its conserved C-terminal and unique N-terminal domains, and their implications for protein interactions and phase separation.

Key Findings:

• ANXA11 co-aggregates with TDP-43 in all cases of FTLD-TDP type C.
• ANXA11 is implicated in familial and sporadic cases of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD).
• The N-terminal domain of ANXA11 is crucial for its interactions with other proteins.

Interpretation:

ANXA11 is implicated in the pathogenesis of FTLD-TDP type C and potentially other TDP-43-related neurodegenerative diseases.

Limitations:

• ThereviewdoesnotcoverANXA11'srolesbeyondneurodegeneration.

Conclusion:

ANXA11's structural and functional characteristics suggest its role in neurodegenerative processes related to TDP-43 pathology.