Bottom line

For human TAX1BP1 (UniProt Q86VP1), the strongest evidence supports it as a selective-autophagy cargo adaptor / autophagy receptor. Within that broad class, the best-supported proteostasis-related roles are aggrephagy and lysophagy. It also has well-supported roles in xenophagy and mitophagy, but these appear more context-specific than its core identity as a cargo adaptor. I found no strong evidence that TAX1BP1’s primary proteostasis function is autophagosome-lysosome fusion itself; rather, it helps recruit/organize upstream autophagy machinery and cargo. (pmc.ncbi.nlm.nih.gov)

Classification, from strongest to weakest support

1) Selective-autophagy cargo adaptor activity — strongest support

TAX1BP1 is consistently described as a selective autophagy receptor / cargo adaptor that binds ubiquitinated cargo and LC3/GABARAP-family proteins via its ubiquitin-binding and LIR-containing regions. Reviews and mechanistic studies describe SLRs as adaptor-like proteins that tether cargo to the phagophore, and TAX1BP1 is repeatedly placed in that group. A 2024 mechanistic paper further emphasizes TAX1BP1’s interactions with RB1CC1/FIP200 and ATG8-family proteins, reinforcing its receptor/adaptor identity rather than a late fusion factor. (pmc.ncbi.nlm.nih.gov)

2) Macroautophagy — supported, but as a broader pathway context

TAX1BP1 participates in selective macroautophagy, especially in cargo-specific autophagic sequestration. Studies show TAX1BP1 can trigger LC3 lipidation in reconstituted systems and can recruit the autophagy initiation machinery to cargo, which is macroautophagy-related but still in the selective-autophagy subclass. So “macroautophagy” is true in a broad sense, but it is less precise than “selective-autophagy cargo adaptor.” (pmc.ncbi.nlm.nih.gov)

3) Lysophagy — strong proteostasis-relevant evidence

Among specific cargo contexts, TAX1BP1 has strong evidence for lysophagy. Quantitative proteomics studies found TAX1BP1 recruited to damaged lysosomes, and functional work showed TAX1BP1 is required for efficient lysophagic flux. The mechanism involves TAX1BP1’s SKICH domain and interactions with TBK1 and RB1CC1/FIP200, which places it firmly in autophagy initiation around damaged lysosomes. This is one of the cleanest proteostasis phenotypes for TAX1BP1. (pubmed.ncbi.nlm.nih.gov)

4) Aggrephagy — strong and arguably the most proteostasis-specific substrate class

For misfolded-protein handling, TAX1BP1 has strong support in aggrephagy. Reviews summarize that TAX1BP1 contributes to clearance of protein aggregates, and 2024 work specifically describes TAX1BP1 as an autophagy initiator that advances aggrephagy from cargo collection to sequestration. Another recent study shows TAX1BP1 recruits FIP200 in p62-aggregate aggrephagy. If your focus is narrow proteostasis, this is likely the most relevant substrate-specific function besides lysophagy. (pmc.ncbi.nlm.nih.gov)

5) Xenophagy — real and well supported, but more context-dependent

TAX1BP1 was shown to be required for clearance of Salmonella Typhimurium by autophagy, i.e. xenophagy, and is recruited to cytosolic bacteria. However, this function is one branch of its selective-autophagy repertoire rather than the dominant proteostasis role. It is meaningful, but not the most convincing “core” function if you are choosing one label for TAX1BP1 overall. (pmc.ncbi.nlm.nih.gov)

6) Mitophagy — supported, but not the strongest overall identity

TAX1BP1 is repeatedly implicated in Parkin/PINK1-dependent mitophagy. Reconstitution experiments used TAX1BP1 as one of the mitophagy cargo receptors capable of driving cargo-induced LC3 lipidation, and proteogenetic analyses of PARK2-dependent mitophagy identified TAX1BP1 as a receptor recruited to ubiquitinated mitochondria. That said, the mitophagy literature generally places TAX1BP1 alongside other receptors such as OPTN and NDP52, rather than uniquely emphasizing TAX1BP1. (pmc.ncbi.nlm.nih.gov)

7) Autophagosome-lysosome fusion — weakest / not primary

I did not find strong evidence that TAX1BP1 is a core autophagosome-lysosome fusion factor. Some papers mention roles in amphisome formation or recruitment of motor/adaptor machinery, but that is distinct from directly mediating autophagosome-lysosome fusion. The current evidence supports TAX1BP1 more as an upstream cargo adaptor and autophagy initiator than as a fusion executor. (pmc.ncbi.nlm.nih.gov)

Distinguishing core proteostasis roles from innate-immune signaling

TAX1BP1 is also involved in innate-immune and inflammatory signaling pathways, including regulation of NF-κB-, TNF-, TLR-, RIG-I-, and antiviral pathways. Those functions are real, but they are separable from its core proteostasis role as an autophagy receptor/cargo adaptor. Reactome and reviews explicitly list TAX1BP1 as participating in inflammatory and antiviral processes as well as selective autophagy regulation. (reactome.org)

Overall conclusion

If you need one best label for human TAX1BP1 in a proteostasis-focused analysis, choose:

Selective-autophagy cargo adaptor / autophagy receptor
with strongest substrate-context evidence in aggrephagy and lysophagy, and additional evidence for xenophagy and mitophagy.
It is not best classified primarily as an autophagosome-lysosome fusion factor. (pmc.ncbi.nlm.nih.gov)

If you want, I can turn this into a ranked evidence table with columns for mechanism, substrate, assay type, and strength of evidence.