| Study/Reference | Experimental approach | Key finding | Functional implication |
|---|---|---|---|
| Roodveldt et al., 2009, *EMBO Journal* | RNAi knockdown of **hip-1/T12D8.8** in a transgenic *C. elegans* α-synuclein-YFP inclusion model; confocal quantification of inclusions in young adults | **hip-1 RNAi increased α-synuclein inclusions 2.3-fold** relative to control (**P**<0.0001) (pqac-00000022, pqac-00000023) | hip-1 is required in vivo to suppress proteotoxic α-synuclein aggregation and supports proteostasis in the worm cytosol (pqac-00000022, pqac-00000024) |
| Roodveldt et al., 2009, *EMBO Journal* | Double RNAi knockdown of **hsp70 (C12C8.1) + hip-1 (T12D8.8)** in the same *C. elegans* α-synuclein model | Double knockdown **reduced inclusions by ~60% compared with hip-1 knockdown alone**, approaching the hsp70-knockdown phenotype (pqac-00000023, pqac-00000024) | Provides genetic evidence that hip-1 acts **through/with Hsp70**, functioning upstream to modulate Hsp70-dependent anti-aggregation activity (pqac-00000023) |
| Roodveldt et al., 2009, *EMBO Journal* | In vitro α-synuclein aggregation assay with purified proteins; ThT fluorescence, TEM, and solubility analysis in the presence of **Hip + Hsp70 + ATP** | Addition of **Hip to Hsp70 in the presence of ATP completely suppressed conversion of α-synuclein into amyloid species** and maintained Hsp70 and α-synuclein in soluble form (pqac-00000022, pqac-00000025) | hip-1/Hip is an **Hsp70 co-chaperone** that prevents Hsp70 co-aggregation and stabilizes anti-amyloid chaperone function under ATP-turnover conditions (pqac-00000022, pqac-00000023) |
| Li et al., 2013, *Nature Structural & Molecular Biology* | Structural and biochemical characterization of mammalian Hip/ST13, including domain mapping and Hsp70-binding analysis | Hip’s **TPR domain binds the Hsp70 nucleotide-binding domain (NBD)** and forms a **bracket over the nucleotide-binding cleft**, stabilizing the **ADP-bound** state; Hip preferentially binds ADP-Hsp70 (KD ~8–10 µM) (pqac-00000013, pqac-00000030, pqac-00000033) | Explains the likely molecular mechanism of worm hip-1: a conserved Hip-family co-chaperone that **slows ADP release, prolongs substrate holding, and prevents premature substrate release** (pqac-00000011, pqac-00000013, pqac-00000032) |
| Juszkiewicz et al., 2025, *Molecular Biology of the Cell* | Biochemical and mechanistic analysis of St13 on mitochondrial precursor proteins and mitochondrial targeting signals (MTSs) | **St13 directly engages mitochondrial targeting signals** via its STI1 domain hydrophobic groove and recruits/retains **Hsc70/Hsp90** on precursors to maintain import competence (pqac-00000034, pqac-00000035, pqac-00000036) | Expands Hip-family function beyond generic proteostasis: hip-1-like proteins can act in **mitochondrial precursor triage/import competence**, suggesting additional conserved roles for worm hip-1 inferred from domain architecture (pqac-00000034, pqac-00000036) |


*Table: This table summarizes the main experimental findings supporting functional annotation of C. elegans hip-1 and its orthologous Hip/ST13 mechanism. It links worm genetic evidence to conserved biochemical and structural studies that explain how HIP-1 acts as an Hsp70 co-chaperone.*