### KLHL22 Gene Overview

**Gene Symbol**: KLHL22  
**Location**: Human chromosome 17

**Function**: KLHL22 encodes a substrate-specific adapter protein that is part of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex. KLHL22 facilitates protein interactions and ubiquitination processes that are crucial for maintaining various cellular functions, including regulating the mitotic spindle assembly checkpoint and mTOR signaling pathways.

### 1. Other Associated Genes
While KLHL22 is particularly linked to PLK1 and DEPDC5, it has also been implicated in interactions with other proteins in signaling pathways, though not all are explicitly mentioned. Some possible associations include:
- **GATOR1 complex genes**: May interact indirectly with **DEPDC5**, **NPRL2**, and **NPRL3** as part of its role in amino acid sensing.
- **CUL3**: The cullin protein that is part of the E3 ligase complex.
- **RBX1**: Another component of the ubiquitin ligase complex.
- Other 14-3-3 family proteins, which assist in diverse signaling pathways and stress responses.

### 2. Aging and Age-Related Diseases
Although specific studies detailing the direct role of KLHL22 in aging or age-related diseases may be limited, its involvement in the mTOR pathway suggests potential associations. The mTOR pathway regulates cell growth, proliferation, and metabolism, processes that are known to have implications in aging and age-related diseases such as:
- **Cancer**: Dysregulation of PLK1 via KLHL22 may affect cancer cell division and tumor progression.
- **Neurodegenerative Diseases**: Changes in autophagy, which is regulated through mTOR, can lead to accumulation of damaged proteins, a hallmark of neurodegeneration.
- **Metabolic Disorders**: Aberrant signaling in the mTOR pathway is associated with age-related changes in insulin sensitivity and metabolism.

### 3. Drug Interactions
Currently, there are no direct drugs specifically targeting KLHL22 cited in literature. However, drugs that influence the mTOR pathway or protein degradation via the ubiquitin-proteasome system may indirectly affect KLHL22's function. Drug classes include:
- **mTOR inhibitors**: Such as rapamycin and its analogs (rapalogs), which can affect downstream processes in which KLHL22 is implicated.
- **Proteasome inhibitors**: Such as bortezomib, may indirectly influence the functions related to ubiquitin ligase complexes involving KLHL22.
- **14-3-3 protein modulators**: Being a binding partner of KLHL22, any small molecular inhibitors affecting these proteins might have downstream effects.

### 4. Pathways and Biological Processes
KLHL22 is involved in several critical biological processes and pathways, such as:
- **Ubiquitin-Mediated Proteolysis**: It acts as an E3 ligase adapter, involved in tagging proteins for degradation.
- **Cell Cycle Regulation**: Particularly at the mitotic spindle assembly checkpoint, ensuring proper chromosome alignment and segregation.
- **mTOR Signaling Pathway**: Acts as an amino acid-dependent activator that influences cell growth, metabolism, and autophagy.
- **Response to Leucine**: Allowing cellular adaptations to nutrient availability, with implications for growth and metabolism.

In summary, KLHL22 plays a multifaceted role in cellular protein homeostasis, signaling pathways related to growth and stress response, and potentially in the context of aging and age-related diseases through its involvement in critical biological processes. More research may uncover additional associations and therapeutic targets connected to KLHL22.