The PLEKHG3 gene (Pleckstrin Homology Domain-Containing, Family G, Member 3) encodes a protein that acts as a guanine nucleotide exchange factor (GEF) for members of the Rho family of small GTPases, particularly RAC1 and CDC42. The role of PLEKHG3 in cellular signaling pathways has implications for cell polarity, motility, and cytoskeletal dynamics.

### 1. Associated Genes
While PLEKHG3 directly interacts with RAC1 and CDC42, it is indirectly associated with a number of other genes and proteins involved in related pathways, including:
- **RHOA** — another Rho family member, often involved in cytoskeletal organization.
- **ACSL4** — associated with lipid metabolism and cell signaling.
- **ARP2/3 complex** — involved in actin nucleation and polymerization.
- **PAK1/PAK2** — p21-activated kinases that interact with RAC1 and CDC42 in various signaling pathways.

### 2. Aging and Age-Related Diseases
Research into the specific role of PLEKHG3 in aging and age-related diseases is limited; however, its involvement in cell motility and polarity suggests potential implications in:
- **Cancer**: Abnormal cell motility and signaling due to mutations or dysregulation of GEFs, including PLEKHG3, can contribute to tumor progression and metastasis in various cancers.
- **Neurodegenerative Diseases**: Disruptions in signaling pathways involving small GTPases can also be linked to conditions like Alzheimer’s disease, where changes in cytoskeletal dynamics play a critical role in neuronal function and survival.

### 3. Drug Interactions
The PLEKHG3 gene does not have widely recognized direct drug interactions in the literature as of October 2023. However, small GTPase signaling pathways, particularly those involving RAC1 and CDC42, can be influenced by:
- **Cytoskeletal inhibitors**: Compounds that target the actin cytoskeleton (e.g., cytochalasins).
- **Rho kinase inhibitors**: Drugs that inhibit Rho-associated protein kinases may indirectly affect the signaling pathways mediated by PLEKHG3.

### 4. Pathways and Biological Processes
PLEKHG3 is involved in multiple biological processes, including:
- **Actin Cytoskeleton Organization**: PLEKHG3 enhances actin polymerization, essential for maintaining cell shape and motility.
- **Rho GTPase Signal Transduction**: As a GEF for RAC1 and CDC42, it regulates their activation, which is critical for various signaling pathways that control cellular responses to external stimuli.
- **Cell Polarity and Migration**: PLEKHG3 is implicated in processes that dictate how cells orient themselves and move in response to their environment.
- **Cell Adhesion**: Involvement in dynamics related to cell adhesion can influence tissue integrity and migration.

In summary, PLEKHG3 is a key player in cellular signaling networks, influencing cell behavior through its interactions with small GTPases. Its relevance in diseases, particularly cancer and potentially neurodegeneration, reflects its importance in maintaining normal cellular functions and dynamics. Further research may illuminate more specific roles of this gene in aging and drug responses.