This study presents a genome-scale screening platform for long noncoding RNAs (lncRNAs) using Cas13d/CasRx, overcoming the limitations of previous methods such as CRISPR-Cas9 and CRISPR interference (CRISPRi). The platform, named Albarossa, targets 24,171 lncRNA genes and supports high-throughput mapping of lncRNA dependencies across various cancer types. Key advancements include: 1. **Optimization of CasRx System**: The CasRx system was optimized for efficient RNA targeting and reduced off-target effects, ensuring robust and specific screening. 2. **Library Design**: A comprehensive lncRNA library was designed, incorporating criteria for screening feasibility, scalability, and broad representation across tumor entities. The library targets 24,171 lncRNA genes, capturing a wide range of functional and context-specific lncRNAs. 3. **Pan-Cancer Screening**: The platform was applied to three cancer types (glioblastoma, lung cancer, and pancreatic ductal adenocarcinoma), identifying numerous context-specific and common essential lncRNAs. 4. ** Validation and Analysis**: The screening results were validated through various assays, including competition assays, clonogenic assays, and serial quantification of proliferation over time. The findings confirmed the functionality and specificity of the identified lncRNAs. 5. **Comparison with Previous Methods**: The CasRx-based screens outperformed previous methods in terms of hit discovery efficiency, specificity, scalability, and broad library applicability. They identified a higher number of core and common lncRNA vulnerabilities compared to CRISPRi and Cas9-based deletion methods. The study highlights the potential of CasRx for systematic exploration of lncRNA biology in health and disease, providing a powerful tool for future research in this field.This study presents a genome-scale screening platform for long noncoding RNAs (lncRNAs) using Cas13d/CasRx, overcoming the limitations of previous methods such as CRISPR-Cas9 and CRISPR interference (CRISPRi). The platform, named Albarossa, targets 24,171 lncRNA genes and supports high-throughput mapping of lncRNA dependencies across various cancer types. Key advancements include: 1. **Optimization of CasRx System**: The CasRx system was optimized for efficient RNA targeting and reduced off-target effects, ensuring robust and specific screening. 2. **Library Design**: A comprehensive lncRNA library was designed, incorporating criteria for screening feasibility, scalability, and broad representation across tumor entities. The library targets 24,171 lncRNA genes, capturing a wide range of functional and context-specific lncRNAs. 3. **Pan-Cancer Screening**: The platform was applied to three cancer types (glioblastoma, lung cancer, and pancreatic ductal adenocarcinoma), identifying numerous context-specific and common essential lncRNAs. 4. ** Validation and Analysis**: The screening results were validated through various assays, including competition assays, clonogenic assays, and serial quantification of proliferation over time. The findings confirmed the functionality and specificity of the identified lncRNAs. 5. **Comparison with Previous Methods**: The CasRx-based screens outperformed previous methods in terms of hit discovery efficiency, specificity, scalability, and broad library applicability. They identified a higher number of core and common lncRNA vulnerabilities compared to CRISPRi and Cas9-based deletion methods. The study highlights the potential of CasRx for systematic exploration of lncRNA biology in health and disease, providing a powerful tool for future research in this field.