### USP15 Gene Overview

**Gene Symbol:** USP15

**Description:** The USP15 gene encodes a member of the ubiquitin-specific protease (USP) family of enzymes, which are critical for the post-translational modification of proteins through the removal of ubiquitin chains. This process is essential for various biological functions, including protein degradation, signal transduction, and regulation of protein functions.

### 1. Associated Genes
While the summaries focus primarily on the functions of USP15 with specific substrates, it may also be associated with:

- **SMAD Proteins** (e.g., SMAD1, SMAD2, SMAD3): Involved in TGF-beta signaling.
- **TGF-beta Receptors** (e.g., TGFBR1): Involved in TGF-beta signaling pathway regulation.
- **NFKBIA:** A negative regulator of NF-kappa-B activity.
- **CARD9:** Related to antifungal immunity.

There may be other genes involved in the pathways regulated by USP15, but their associations can vary based on cellular context and environmental conditions.

### 2. Details Related to Aging or Age-Related Diseases
Research suggests that USP15 has potential roles in age-related processes:

- **Cellular senescence:** Changes in ubiquitin-proteasome system functions are often linked to aging. USP15 may influence the stability and degradation of proteins involved in senescence.
- **Neurodegenerative disorders:** Misregulation of protein ubiquitination has been implicated in conditions such as Alzheimer's disease. The deubiquitinating functions of USP15 could impact the clearance of misfolded proteins.
- **Cancer:** Alterations in the TGF-beta signaling pathway and ubiquitin-mediated proteolytic pathways involving USP15 can contribute to tumor progression and metastasis, potentially linking it to age-related carcinogenesis.

### 3. Drug Interactions
There are currently no widely recognized specific drugs targeting USP15 directly. However, drugs that modulate the ubiquitin-proteasome system (e.g., proteasome inhibitors like Bortezomib) might indirectly influence USP15 activity or its pathway. Researchers are investigating targeted therapeutics that affect deubiquitinating enzymes generally, which could impact the activity of USP15.

### 4. Pathways and Biological Processes
USP15 is involved in multiple key pathways and biological processes:

- **TGF-beta Signaling Pathway**: Its role in promoting the deubiquitination of receptor-activated SMAD proteins and TGF-beta receptors enhances TGF-beta signaling.
- **NF-kappa-B Signaling**: Regulates inflammation and immune response by deubiquitinating NFKBIA.
- **Mitophagy Regulation**: Interacts with parkin and influences mitochondrial turnover.
- **Endosomal Pathway**: Mediates deubiquitination of substrates like SQSTM1, affecting endosome organization and vesicle transport.
- **Histone Modification**: Potential role in regulating gene expression and DNA repair through deubiquitination of histone H2B.
- **Antifungal Immunity**: Modulates immune response by deubiquitinating CARD9.

In summary, USP15 is a critical enzyme with roles in ubiquitin-mediated signaling and regulation of multiple pathways related to development, immune response, aging, and potentially in various diseases, particularly cancer and neurodegenerative disorders. Understanding its functions and interactions offers insights into the complex biology of ubiquitination and its implications in health and disease.