### PSMD13 Gene Overview

**Gene Symbol**: PSMD13  
**Alternative Names**: 26S proteasome non-ATPase subunit 13, Rpn13  
**Location**: Chromosome 6 (6p21.1)  

### 1. Associated Genes

PSMD13 is linked to several other genes, particularly those involved in proteasome function and ubiquitin-mediated proteolysis. Some associated genes include:

- **PSMC proteins**: These are part of the ATPase component of the 26S proteasome, including PSMA and PSMD family members which play critical roles in proteasome assembly and function.
- **UBE2 series**: Ubiquitin-conjugating enzymes (e.g., UBE2C, UBE2D) are involved in the ubiquitination process, marking proteins for degradation by the proteasome, which is closely related to the function of PSMD13.
- **CAST**: Calpain small subunit (CAST) also interacts with the ubiquitin-proteasome system and may be functionally connected to PSMD13.
- **UBR family**: UBR1 and UBR2, involved in recognizing and targeting proteins for degradation, may have interactions relevant to the function of PSMD13.

### 2. Aging and Age-Related Diseases

Research indicates that the proteasome pathway, including PSMD13, plays a crucial role in aging and age-related diseases. Some details include:

- **Protein Homeostasis**: PSMD13 is implicated in maintaining protein quality control. Disruptions in proteasome function can lead to the accumulation of damaged or misfolded proteins, contributing to the aging process and age-related disorders such as neurodegenerative diseases (Alzheimer's and Parkinson's).
- **Inflammation**: The role of PSMD13 in processing proteins involved in inflammatory responses may link it to age-related chronic inflammatory diseases.
- **Cellular Senescence**: Impairment of the proteasome results in an accumulation of cell cycle inhibitors, contributing to the onset of cellular senescence, a hallmark of aging.
  
### 3. Drug Interactions

PSMD13 has been associated with several drugs and drug classes, especially those targeting proteasome activity:

- **Bortezomib (Velcade)**: A proteasome inhibitor used primarily in the treatment of multiple myeloma and certain types of lymphoma. It directly impacts proteasome function which includes subunits like PSMD13.
- **Carfilzomib**: Another proteasome inhibitor with therapeutic uses similar to Bortezomib. Its function may influence pathways involving PSMD13.
- **Ixazomib**: An oral proteasome inhibitor utilized in treating multiple myeloma, affecting the same pathways.

### 4. Pathways and Biological Processes

PSMD13 is involved in a variety of crucial cellular pathways and processes:

- **Ubiquitin-Proteasome Pathway**: PSMD13 is essential for the assembly and functioning of the 26S proteasome, which degrades ubiquitinated proteins.
- **Cell Cycle Regulation**: Through proteolytic pathways, PSMD13 plays a role in regulating the cell cycle, particularly through the degradation of cyclins and cyclin-dependent kinase inhibitors.
- **DNA Repair**: PSMD13 is implicated in pathways essential for DNA damage response, where the degradation of specific proteins is necessary to maintain genomic stability.
- **Antigen Processing and Presentation**: Contributes to the immunoproteasome function, facilitating the processing of intracellular proteins for presentation by MHC class I molecules, critical for immune responses.

In summary, PSMD13 is a pivotal component of the 26S proteasome, playing crucial roles in protein degradation, cellular homeostasis, and involvement in various biological processes. Its interactions and function relate significantly to aging and pathology, making it a relevant target for exploring therapeutic strategies in age-related diseases.